This is a competing renewal proposal of our previous grant application. The objective of the previous grant application was to investigate the effects of the use of ultrasound to enhance polymeric drug delivery and drug permeation through skin. In this past grant period, we investigated the effects of polymer molecular weight, cavitation, temperature, solution gas content, and other factors on ultrasound induced polymeric drug delivery; we showed that ultrasound could enhance transdermal drug delivery, that it could act as a trigger to terminate the activity of controlled release implants, and that it could provide a new rapid method of achieving protein blotting from electrophoretic gels. We believe that these studies will have wide applicability in a number of areas for ultrasound-assisted transport and, indeed, many of these avenues of application are now being pursued in other laboratories. In the current grant application, we wish to focus our attention on one of these areas- ultrasound-assisted transdermal drug delivery with special emphasis on protein delivery in part due to the reviewers' previous comments-because of the great impact that can now be made in this area. The specific goals of this proposal include: 1. Understanding the mechanisms of transdermal flux enhancement due to ultrasound. 2. Understand the dependence of sonophoresis on ultrasound parameters. 3. Investigate safety issues of sonophoresis. 4. Modeling ultrasound-mediated enhancement and transdermal fluxes.